Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

Patient monitoring
Cases of serious hypotension have been reported during and immediately following vernakalant infusion. Patients should be carefully observed for the entire duration of the infusion and for at least 15 minutes after completion of the infusion with assessment of vital signs and continuous cardiac rhythm monitoring.

If any of the following signs or symptoms occurs, the administration of vernakalant should be discontinued and these patients should receive appropriate medical management:
• A sudden drop in blood pressure or heart rate, with or without symptomatic hypotension or bradycardia
• Hypotension
• Bradycardia
• ECG changes (such as a clinically meaningful sinus pause, complete heart block, new bundle branch block, significant prolongation of the QRS or QT interval, changes consistent with ischaemia or infarction and ventricular arrhythmia)

If these events occur during the first infusion of vernakalant, patients should not receive the second dose.

The patient should be further monitored for 2 hrs after the start of infusion and until clinical and ECG parameters have stabilised.


Precautions before infusion
Prior to attempting pharmacological cardioversion, patients should be adequately hydrated and haemodynamically optimized and if necessary patients should be anticoagulated in accordance with treatment guidelines. In patients with uncorrected hypokalaemia (serum potassium of less than 3.5 mmol/l), potassium levels should be corrected prior to use of vernakalant .


Hypotension
Hypotension can occur in a small number of patients (vernakalant 5.7%, placebo 5.5% in the first 2 hours post-dose). Hypotension typically occurs early, either during the infusion or early after the end of the infusion, and can usually be corrected by standard supportive measures.
Uncommonly, cases of severe hypotension have been observed. Patients with congestive heart failure (CHF) have been identified as a population at higher risk for hypotension. (see section 4.8).

The patient is required to be monitored for signs and symptoms of a sudden decrease in blood pressure or heart rate for the duration of the infusion and for at least 15 minutes after the completion of the infusion.
Congestive heart failure
Patients with CHF showed a higher overall incidence of hypotensive events, during the first 2 hours after dose in patients treated with vernakalant compared to patients receiving placebo (13.4% versus 4.7%, respectively). Hypotension reported as a serious adverse experience or leading to medicinal product discontinuation occurred in CHF patients following exposure to vernakalant in 1.8% of these patients compared to 0.3% in placebo.

Patients with a history of CHF showed a higher incidence of ventricular arrhythmia in the first two hours post dose (6.4% for vernakalant compared to 1.6% in placebo). These arrhythmias typically presented as asymptomatic, monomorphic, non-sustained (average 3-4 beats) ventricular tachycardias.

Due to the higher incidence of the adverse reactions of hypotension and ventricular arrhythmia in patients with CHF, vernakalant should be used cautiously in haemodynamically stable patients with CHF functional classes NYHA I to II. There is limited experience with the use of vernakalant in patients with previously documented LVEF ≤ 35%. Its use in these patients is not recommended. The use in CHF patients corresponding to NYHA III or NYHA IV is contraindicated (see section 4.3).

Valvular heart disease
In patients with valvular heart disease, there was a higher incidence of ventricular arrhythmia events in vernakalant patients until 24 hours after dosing. Within the first 2 hours, ventricular arrhythmia occurred in 6.4 % of patients treated with vernakalant versus none after placebo.These patients should be monitored closely.

Atrial flutter
Vernakalant was not found to be effective in converting typical primary atrial flutter to sinus rhythm. Patients receiving vernakalant have a higher incidence of converting to atrial flutter within the first 2 hours post-dose. This risk is higher in patients who use Class I antiarrhythmics (see section 4.8). If atrial flutter is observed as secondary to treatment, continuation of infusion should be considered (see section 4.2). In post-marketing experience rare cases of atrial flutter with 1:1 atrioventricular conduction are observed.

Other diseases and conditions not studied
Vernakalant has been administered to patients with an uncorrected QT less than 440 ms without an increased risk of torsade de pointes.

Furthermore, it has not been evaluated in patients with clinically meaningful valvular stenosis, hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy, or constrictive pericarditis and its use cannot be recommended in such cases. There is limited experience with vernakalant in patients with pacemakers.

As the clinical trial experience in patients with advanced hepatic impairment is limited, vernakalant is not recommended in these patients.

There are no clinical data on repeat doses after the initial and second infusions.

Electrical cardioversion
Direct-current cardioversion may be considered for patients who do not respond to therapy.
There is no clinical experience with direct-current cardioversion under 2 hours post-dose.
Use of AADs (antiarrhythmic drugs) prior to or after vernakalant
Vernakalant cannot be recommended in patients previously administered intravenous AADs (class I and III) 4-24 hours prior to vernakalant due to lack of data. It must not be administered in patients who received intravenous AADs (class I and III) within 4 hours prior to vernakalant (see section 4.3).
Vernakalant should be used with caution in patients on oral AADs (class I and III), due to limited experience. Risk of atrial flutter may be increased in patients receiving class I AADs (see above).

There is limited experience with the use of intravenous rhythm control antiarrhythmics (class I and class III) in the first 4 hours after vernakalant administration, therefore these agents must not be used within this period (see section 4.3).

Resumption or initiation of oral maintenance antiarrhythmic therapy can be considered starting 2 hours after vernakalant administration.

Sodium content
This medicinal product contains 32 mg sodium per 200 mg vial, equivalent to 1.6 % of the WHO recommended maximum daily intake of 2 g sodium for an adult.
This medicinal product contains 80 mg sodium per 500 mg vial, equivalent to 4 % of the WHO recommended maximum daily intake of 2 g sodium for an adult.

Effects on Driving

4.7   Effects on ability to drive and use machines

Vernakalant has minor to moderate influence on the ability to drive and use machines.
Dizziness has been reported within the first 2 hours after receiving it (see section 4.8).